骨髓间充质干细胞(MSCs)在创面修复过程中扮演重要角色，但其在创伤后被动员、归巢及分化、分泌行为的调控因素尚未阐明。研究证明：神经内分泌因素在皮肤的自我更新、修复与再生中起重要作用；且肾素-血管紧张素系统（RAS）作为重要的应激激素与皮肤的损伤修复和再生密切相关，其与骨髓MSCs的关联性已倍受关注。我们最近研究发现：创伤后RAS被激活，组织和循环中的RAS重要成份水平升高，结合既往相关研究，推测：RAS对骨髓MSCs动员、归巢及分化、分泌行为存有调控作用，可能是RAS影响创伤愈合的机制之一。研究以小鼠骨髓MSCs为对象，结合皮肤缺损创面愈合模型，采用体外细胞培养、EGFP转基因小鼠骨髓MSCs输入、骨髓功能抑制等技术方法证明之，并初步探讨RAS对骨髓MSCs生物学行为影响的分子机制。研究结果将有助于阐明神经内分泌因素调控皮肤损伤修复的机制，并为丰富创面促愈手段，提高修复质量提供理论基础。

Optimum healing of a cutaneous wound requires a well-orchestrated integration of the complex biological and molecular events of cell migration and proliferation, and of extracellualr matrix deposition and remodeling. Several studies in recent years suggest that bone marrow derived stem cell such as mesenchymal stem cells may be involved in these processes, contributing to skin cells or releasing regulatory cytokines. Bone mrrow derived mesenchymal stem cells may be mobilized to leave the bone marrow, home to injured tissues and participate in wound repair and regeneration. However, the mechanism involved in these processes has not been fully understood. It has been demonstrated that skin is a source of and target organ for neuroendocrinological hormone. Growing evidence has revealed that renin-angiotensin system (RAS) as one of important hormones is closely associated with cutaneous wound repair and regeneration. Moreover, the existence of complete RAS in bone marrow has been recently demonstrated. More recently, we have found increased the production of angiotensin II, a key peptide of RAS in injured tissue and circulating system after wounding. Therefore, we hypothesize that the activited RAS as an injury-inducible messenger might not only stimulate the cell proliferation and mobilization in wounded sites, but also induce bone mrrow derived mesenchymal stem cell to leave the bone marrow, home to injured tissues and participate in wound repair and regeneration, which may be one of mechanisms that RAS infulences wound healing. To prove our hypothesis, we designed the experiment. In the present study, we will develop mouse full-thickness skin wound model to observe the effect of RAS on the mobilization, homing and secretion of bone marrow derived mesenchymal stem cells. We also will use the mice with damaged bone marrow function to develop cutaneous wound model, and infuse the bone marrow derived mesenchymal stem cells from EGFP transgenic mice into widetype mice to further observe the effct of RAS on the mobilization, homing and transdifferentiation of bone marrow derived mesenchymal stem cells. Meanwhile， mouse bone marrow mesenchaymal stem cells will be cultured to examine the effect of RAS on the mobilization, homing, secretion and transdifferentiation of bone marrow derived mesenchymal stem cells. Based on above-designed experiment, we will try to reveal the molecular mechanisms by which RAS as an important injury-inducible messenger influences wound healing through recruiting bone-derived mesenchymal stem cells into wounded sites. This study will be helpful to understanding the cellular and molecular mechanisms of wound healing, as well as improving the outcome of wound repair.